Essential Drugs: Looking back and exploring the future

Dr. John Dunne
Former Director
Division of Drug Management & Policies and Editor
WHO Drug Information

The World Health Organization's concept of essential drugs is now some twenty years old. It was launched "to advice Member States on the selection and procurement, at reasonable cost, of essential drugs of established quality corresponding to their national needs." Essential drugs were defined as those that satisfy the health care requirements of the majority of the population, and a model list, first issued by WHO in 1977, has since been updated biennially by a WHO Expert Committee(1). This has helped to ingrain within national health administrations, and among health care workers in general, the principle that a selected core of essential drugs should be available at all times and at every level within the health-care system.

The essential drugs concept has provided a means by which governments and donor agencies can plan and monitor drug procurement. It remains vital, none the less, to differentiate between acceptance in principle of the concept by governments, and its implementation. This was one of the fundamentals voiced within a workshop recently convened to review what promotion of the concept has so far achieved and, more specifically, to explore how far those medicines now on the list satisfy contemporary needs(2). Participants - the majority of whom had long been involved at first hand in the development of WHO's essential drugs concept - were particularly concerned that more should be known about its impact within the least developed countries where per capita expenditure on health remains less than US$10 annually.

WHO, it was acknowledged, has produced useful materials both to support the implementation of the essential drugs concept within the context of a national drugs policy(3), and to monitor the implementation and outcome of relevant programmes(4). However, recognizing that the cost of effective monitoring is prohibitive where it is most needed, it was stressed by the group that efforts should be reinforced to establish commitment to the concept among health professionals, their teachers and the public at large.

The group had no doubt that the concept retains its original relevance. Indeed, as governments everywhere are forced into containing health care budgets, this relevance is broadening to embrace countries at every level of development. It was considered important that a distinction be drawn between the essential drugs concept, which is concerned with assuring access to medicines throughout the health care system, and the evolution of managed health care schemes directed specifically to cost containment.

The participants also agreed that promotion of the concept would be enhanced if the model list were more informative. Ideally, it was felt, information should not be directed solely to the least affluent countries; it should also assist decision-making in countries at other levels of development. Most importantly, WHO could profitably provide more explaination on the reasons for listing - and perhaps excluding - specific drugs. In contrast to a recent proposal from the World Bank(5), no support was registered for arbitrarily excluding selected categories of drugs from the list. The stated objective of "Health for All" should remain the guiding principle, but there should be no encroachment upon the freedom of national authorities to interpret this advice in the best interests of their populations.

For instance, even though many countries are not yet in a position to provide an effective cancer programme, the group strongly favoured the retention of a short list of drugs used in the management of common cancers. It was not prepared to countenance the option of providing only for palliative care. In the same vein, participants agreed that encouragement should be offered to national authorities to expand the "common core" of essential drugs, as circumstances permit, to accommodate the needs of patients with severe but uncommon diseases. The operation of an essential drug policy, they maintained, should never be perceived as an expedient for ignoring legitimate minority needs.

Much discussion during the workshop centred on the evolution of list over the past twenty years. Changes in successive revisions of the list provide a cogent commentary both on innovative pharmaceutical achievement and on objectives yet to be realized in therapeutic and prophylactic medicine. Since the first list was published, some important lacunae have been eliminated, many in the realm of tropical infectious disease. In the 1970s, neither ivermectin nor eflornithine - later to become milestone in the management of onchocerciasis and African sleeping sickness - had been developed. Important progress has also been made in developing antimalarials drugs, but the rapid emergence of strains resistant to every one of the agents that have been introduced thus far underscores the need to develop a preventive malaria vaccine. There is optimism that this target may now be achieved. Indeed, in a wider context, there is expectation - given the advent of recombinant technology and monoclonal antibodies - that the means is now at hand to develop an array of vaccines that could greatly alleviate much of the burden of infectious disease now hyperendemic in developing countries.

That such an aim is feasible, given efficient global organization of field activities as well as effective vaccines, has been demonstrated not only by the eradication of smallpox almost 20 years ago, but by the mass polio immunization campaigns now under way throughout the world. Over the past decade, the annual number of reported cases of paralytic poliomyelitis has fallen by 90%, and in 1994 stood at an all-time low of some 4,000 cases worldwide(6). WHO is still on track to realize its declared objective of global eradication of polio by the year 2,000(7).

Meanwhile, it maintains its broader commitment to the global control of infectious diseases that continue to threaten the lives of coutless children in developing countries: hepatitis B vaccine and the triple measles-mumps-rubella vaccine have been added in recent years to the core group of listed immunological products that are proposed for universal immunization(1). Within a relatively short time-frame, it may be possible to extend the list further. Important new vaccines including products directed against rotavirus, the typhoid bacillus and the cholera vibrio, are showing promise in field trials. Others, including the conjugated capsular polysaccharide vaccines developed to counter antibiotic-resistant strains of Streptococcus B and Streptococcus penumoniae, are already available, but at a cost that thus far excludes their inclusion in the list.

Conversely and ominously, the model list also exposes new-found frailties in the capicity of society to defend itself from adverse environmental change. New diseases are emerging at a faster rate than the older ones recede. Environmental pressures, varied in nature, are facilitating the transmission of infectious agents - particularly viruses and subviral agents - across the species barrier between animals and man. Human immuno-deficiency virus, and now, possibly transmission of the agent of bovine spongiform encephalopathy to man are illustrative of a broader risk that extends the horizon of concern to many other zoonotic diseases.

After some 15 years of intensive effort to develop drugs effective against HIV, no antiviral products are as yet included within WHO's model list. Zidovudine, which has been available for more than a decade, has been denied a place because of its cost, its marginal efficacy when used alone and the need for sustained monitoring to assure safe use. With the advent of new antiretroviral drugs and the promise that combination therapy may at last create a truly effective means of treating HIV infection, this policy of exclusion will need to be reviewed. The problem is that the barrier of cost remains impenetrable. For most of the 20 million people carrying HIV, hope of treatment "is likely to be the hope of Tantalus - ever present, but out of reach."(8)

Worse still, this barrier of cost may soon extend to ubiquitous bacterial diseases hitherto readily treatable by inexpensive first-line antibiotics. The emergence of new strains of pathogenic bacteria resistant to all generally- available antibiotic products now present a critical danger to public health. Resistance is now widespread, in both hospital-acquired and community-acquired infections, to all antibiotics included in the original model list. This has forced the introduction of a new category of "reverse antimicrobials" into recent revisions of the model list: products that are "useful for a wide range of infections but, because of the need to reduce the risk of development of resistance and because of their relatively high cost, should not be recommended for unrestricted use"(1).

With some misgiving, the workshop accepted the introduction of these recently- developed antibiotics into the list as inevitable. The cost of these products is formidable everywhere, and it is impossible to use them in a rational sense without the laboratory facilities necessary to identify bacterial pathogens and to screen their susceptibility to antimicrobial agents. To use them blindly is not only wasteful: it is bound to promote further progression of microbial resistance.

Failure to keep community bacterial diseases in check whould have profound implications for society everywhere. The workshop considered it vital that these implications should be reiterated frequently to politicians as well as to policy-makers throughout the health care community. Time is now of the essence. Some patients with pulmonary tuberculosis already harbour multidrug-resistant baccili that render them virtually untreatable. At any time, streptococcal disease could again emerge as a major public health catastrophe. Many patients with serious hospital-acquired infections are now tenously dependent for survival on one or two from malaria continue to rise, and the recent resurgence of cholera in the Americas demonstrates the rapidity with which an acute, readily recognized infectious disease can re-established itself wherever there is frailty within the public health infrastructure.

In concluding its report, the workshop underscores the dangers of leaving discernible and disturbing needs for new antimicrobial drugs and vaccines unfulfilled, and it concludes with an analytic commentary:

Pharmaceutical innovation holds the only tangible solution to these problems. The issue is how to engage committed involvement from the private sector on terms that will retain the commitment of investors. The problems are all to evident. Some of the basic research and development work that is required is highly speculative. Some of the products needed hold scant prospect of commercial return, since they will need to be held in reverse to treat small populations of patients at specific risk. The pharmaceutical industry must consequently be involved from the outset in any discussions of the possible options ... on how an alliance of interests might best be created to assure the necessary investment in this research."

References

  1. Sixth report of the WHO Expert Committee. The use of essential drugs. Technical Report Series, No.850. World Health Organization, Geneva, 1995.
  2. Report of a workshop. Essential drugs and the WHO model list: addressing new issues. Clinical Pharmacology and Therapeutics, 59: 251-257 (1996).
  3. Action Programme on Essential Drugs. Guidelines for developing national drug policies. World Health Organization, Geneva, 1988.
  4. Action programme on Essential Drugs. Indicators for monitoring national drug policies. Unpublished document WHO/DAP 94.12. World Health Organization, Geneva, 1994.
  5. The World Bank. World Development Report 1993. Investing in health. Oxford University Press, New York, 1993, pp. 1-16.
  6. Chanderm J. Subramanyan, S. Mass polio vaccination. Eradication by 2,000 is a realistic goal. British Medical Journal, 312: 11781-1179 (1996).
  7. Robertson, S., Chan, C., Kim-Farley, R., Ward, N. Worldwide status of poliomyelitis in 1986, 1987 and 1988 and plans for global eradication by the year 2,000. World Health Statistics Quarterly, 43: 80-90 (1990).
  8. A solution for AIDS? The Economist. No.7972, 29 June 1996, pp. 15-16.

Source: WHO Drug Information, Vol.10, No.2, 1996, pp.47-49